The field of the invention relates to regulatory T cells (Tregs). In particular, the field of the invention relates to methods for isolating, cultivating, and/or expanding Tregs.
Regulatory T cells (Tregs) are critical regulators of the immune system. Efforts are underway to develop strategies to isolate and expand naturally occurring human Tregs (nTregs) to use as cellular therapies to help control autoimmune disease, graft versus host disease, and organ transplant rejection. nTregs are few in number in the blood and need to be expanded in number significantly to be used as a therapy.
Human B7 homolog (B7-H1), also called programmed cell death ligand 1 (PD-L1) is a member of a growing family of immune proteins that provide signals for both stimulating and inhibiting T cell activation (1-3). Importantly, the interaction of PD-L1 with its ligand PD-1 results in inhibition of T cell receptor (TCR) mediated proliferation and cytokine production predominantly in effector T cell populations. Published work has shown the ability of the PD-L1 to induce naïve T cells to become regulatory T cells (3). As detailed herein, the inventors have used programmed death-ligand 1 (PD-L1) conjugated to paramagnetic beads to promote the expansion of human nTregs that are highly suppressive and potentially effective for the treatment of inflammation and rejection. This approach is applicable to the expansion of both antigen specific as well as antigen nonspecific naturally-occurring Tregs.